The concept of “liquid biopsy” has gained traction in recent years. Instead of taking a sample from solid tissue, liquid biopsies capture cells, extracellular vesicles such as exosomes and/or cell-free molecules such as DNA, RNA, or proteins. These components can be collected in biofluids such as blood (or plasma or serum), urine, sputum, and so forth. The presence of these components can be associated with, for example, cancers, tumors, autoimmune diseases, cardiovascular events, viruses, bacterial or pathogenic infection, or related to a drug response. The molecules of interest are often associated with extracellular bodies such as exosomes, or may be “cell-free” in the fluid.
Liquid biopsies can be conducted using any of several biofluids, and can be minimally invasive (e.g., blood collection by phlebotomy) or non-invasive (urine collection). Liquid biopsies are thus attractive for ease of collection, ease of repeat collection for patient monitoring, higher likelihood of patient acquiescence, familiarity of sample collection to patients, and less specialized collection sites.
One drawback of liquid biopsies is that the concentration of nucleic acid can be relatively low, so that a large volume is needed to obtain sufficient material for downstream analysis. Nucleic acid capture kits and devices are typically designed for small sample volumes, typically in the range of 0.2-1 mL.
While magnetic particles are highly useful for nucleic acid capture, ferromagnetic particles become individually magnetized after exposure to a magnetic field. Serial reuse of magnetic particles after an initial magnetic separation step is currently advised against, because it is believed that the particles will be incapable of effectively binding additional nucleic acid. For example, once the particles are individually magnetized, they form a clump that blocks any unoccupied nucleic acid binding sites.